Various methods have been proposed so far for forming a transdermally absorbable preparation having the improved transdermal absorbability of a drug. First, ion pair formation has been attempted for improving the transdermal absorbability of a drug itself. Some of such attempts are described in, for example, Non-Patent Document 1 and Patent Document 1. Moreover, a patch containing a hydroxyethylpyrrolidine salt of diclofenac has currently been put on the US market as Flector (registered trademark) Patch (Patent Document 2).
Attempts to improve the transdermal absorbability of a drug by devising a solution for dissolving the drug have also been made as alternative methods for improving the transdermal absorbability of a drug. For example, a solvent system of animal or plant oil and fat, polyhydric alcohol, and water (Patent Document 3) or a solvent system of a carboxylic acid ester having 16 to 20 carbon atoms and an alcohol having 2 to 5 carbon atoms (Patent Document 4) has been shown to improve the transdermal absorption of a basic drug or the like.
Non-Patent Document 2 discloses that a lactic acid/ethanol/isopropyl myristate solvent system or a triethanolamine/ethanol/isopropyl myristate solvent system is a favorable solvent system for accelerating the transdermal absorption of a basic drug or an acidic drug.
However, the system of animal or plant fat and oil and polyhydric alcohol separates into two layers and hardly forms a uniform solution. On the other hand, in the ethanol/isopropyl myristate solvent system, which tends to form a uniform solvent system, the solvent composition is variable due to easily volatilized ethanol and hardly produces stable transdermal absorbability. In addition, Patent Document 5 (paragraph 0011) shows that a system of a lower alcohol and a fatty acid ester does not always produce the sufficient effect of accelerating absorption.
Thus, a solvent system that accelerates the transdermal absorption of a drug, has stable solvent composition, and suppresses the decomposition of the drug has been demanded as a solvent system for dissolving a drug to prepare an external preparation.
On the other hand, attempts have also been made to improve the transdermal absorbability of a drug by the addition of a transdermal absorption accelerator. For example, Patent Documents 6 and 8 have reported that the addition of an organic acid salt (e.g., sodium acetate) together with a basic drug improves the transdermal absorbability for a matrix-type patch. Moreover, in Patent Document 7, improvement in the transdermal absorbability for a matrix preparation has been attempted by the addition of an ammonium salt (e.g., diethylamine hydrochloride) together with an acidic drug.
However, more radical improvement in a solvent composition itself has been demanded for further improving the transdermal absorbability of a drug.    Patent Document 1: Japanese Patent Laid-Open No. 2005-82512    Patent Document 2: Japanese Patent No. 3526887    Patent Document 3: Japanese Patent Laid-Open No. 04-99716    Patent Document 4: Japanese Patent Laid-Open No. 06-40947    Patent Document 5: Japanese Patent Laid-Open No. 2007-8871    Patent Document 6: WO 00/61120    Patent Document 7: WO 01/005381    Patent Document 8: WO 01/007018    Non-Patent Document 1: Kazuyoshi Kubo and Tadanori Mayumi, Fragrance Journal, 1998-9, 71-78 (1998)    Non-Patent Document 2: Liang Fang et al., Biol. Pharm. Bull., 25, 1339-1344 (2002)